Introduction: The regulation of receptors is a central concept in pharmacology, covering mechanisms like desensitization, internalization, upregulation and downregulation that determine drug responses. B. Pharm students must understand receptor dynamics—GPCR phosphorylation, arrestin-mediated endocytosis, receptor recycling versus degradation, spare receptor concepts, and signaling bias—to predict tolerance, tachyphylaxis, and therapeutic outcomes. Clinical relevance includes drug resistance, dosing strategies, and adverse effects. Familiarity with terms such as receptor occupancy, Bmax, KD, constitutive activity, inverse agonism, allosteric modulation and receptor oligomerization strengthens pharmacodynamic insight. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which process describes a decrease in receptor responsiveness after continuous or repeated exposure to an agonist?
- Upregulation
- Desensitization
- Potentiation
- Sensitization
Correct Answer: Desensitization
Q2. Homologous desensitization of GPCRs typically involves which initial molecular event?
- Receptor ubiquitination
- Receptor phosphorylation by GRKs
- Receptor acetylation
- Increased receptor gene transcription
Correct Answer: Receptor phosphorylation by GRKs
Q3. Arrestin proteins contribute to receptor regulation mainly by:
- Increasing receptor synthesis
- Blocking G protein coupling and promoting internalization
- Enhancing ligand binding affinity
- Phosphorylating receptors
Correct Answer: Blocking G protein coupling and promoting internalization
Q4. Receptor internalization followed by recycling back to the plasma membrane leads to:
- Permanent loss of receptors
- Transient decrease in surface receptors with potential recovery
- Immediate upregulation of receptor gene expression
- Conversion to nuclear receptors
Correct Answer: Transient decrease in surface receptors with potential recovery
Q5. Downregulation of receptors usually results from:
- Enhanced receptor trafficking to the membrane
- Increased receptor degradation in lysosomes or proteasomes
- Acute receptor phosphorylation without trafficking
- Alternative splicing of receptor mRNA
Correct Answer: Increased receptor degradation in lysosomes or proteasomes
Q6. Upregulation of receptors most commonly occurs in response to:
- Chronic exposure to a high-efficacy agonist
- Chronic blockade by an antagonist
- Acute receptor phosphorylation
- Enhanced arrestin recruitment
Correct Answer: Chronic blockade by an antagonist
Q7. Tachyphylaxis refers to:
- A gradual increase in drug potency over weeks
- A rapid decrease in drug effect after repeated dosing
- Permanently enhanced receptor expression
- Immune-mediated drug hypersensitivity
Correct Answer: A rapid decrease in drug effect after repeated dosing
Q8. Spare receptors (receptor reserve) influence drug response by:
- Requiring higher agonist concentrations for maximal response
- Allowing maximal response at less than full receptor occupancy
- Preventing receptor internalization
- Increasing KD without affecting efficacy
Correct Answer: Allowing maximal response at less than full receptor occupancy
Q9. Biased agonism describes:
- An agonist that only binds one receptor subtype
- An agonist preferentially activating one signaling pathway over another via the same receptor
- A ligand that irreversibly blocks receptor internalization
- Allosteric modulation that increases receptor number
Correct Answer: An agonist preferentially activating one signaling pathway over another via the same receptor
Q10. An inverse agonist differs from a neutral antagonist by:
- Increasing constitutive receptor activity
- Decreasing constitutive receptor activity below basal levels
- Having no effect on receptor activity
- Only binding to internal receptors
Correct Answer: Decreasing constitutive receptor activity below basal levels
Q11. Heterologous desensitization involves:
- Desensitization restricted to the activated receptor only
- Desensitization of multiple receptor types via a common downstream kinase
- Upregulation of unrelated receptors
- Selective increase in receptor mRNA stability
Correct Answer: Desensitization of multiple receptor types via a common downstream kinase
Q12. Which laboratory parameter measures total receptor number in a tissue?
- Kd (dissociation constant)
- Bmax (maximum binding capacity)
- EC50
- Intrinsic efficacy
Correct Answer: Bmax (maximum binding capacity)
Q13. A rightward parallel shift in a dose–response curve without change in maximal effect suggests:
- Noncompetitive antagonism
- Competitive antagonism
- Irreversible receptor downregulation
- Biased agonism
Correct Answer: Competitive antagonism
Q14. Which post-translational modification commonly targets receptors for lysosomal degradation?
- Palmitoylation
- Ubiquitination
- Methylation
- Glycosylation
Correct Answer: Ubiquitination
Q15. Constitutive activity of a receptor means:
- The receptor only signals when agonist-bound
- The receptor exhibits baseline signaling in absence of ligand
- The receptor is permanently internalized
- The receptor cannot be blocked by antagonists
Correct Answer: The receptor exhibits baseline signaling in absence of ligand
Q16. Allosteric modulators regulate receptors by:
- Binding to the same site as the endogenous ligand
- Binding to a distinct site and altering receptor response to the primary ligand
- Causing immediate receptor degradation
- Increasing receptor gene copy number
Correct Answer: Binding to a distinct site and altering receptor response to the primary ligand
Q17. Which mechanism best explains rebound hypersensitivity after abrupt discontinuation of a receptor antagonist?
- Persistent receptor ubiquitination
- Upregulation and supersensitivity of receptors
- Irreversible receptor phosphorylation
- Permanent loss of receptor reserve
Correct Answer: Upregulation and supersensitivity of receptors
Q18. Receptor oligomerization can affect pharmacology by:
- Eliminating ligand binding entirely
- Changing ligand affinity, signaling specificity, or trafficking
- Preventing receptor gene expression
- Converting receptors into enzymes
Correct Answer: Changing ligand affinity, signaling specificity, or trafficking
Q19. Which technique is commonly used to quantify receptor internalization in cell models?
- Western blot for total cellular actin only
- Radioligand binding combined with surface vs. total labeling
- Measuring mRNA levels by RT-PCR alone
- Mass spectrometry of extracellular matrix
Correct Answer: Radioligand binding combined with surface vs. total labeling
Q20. A drug that stabilizes a receptor conformation that preferentially recruits arrestin over G proteins is an example of:
- Neutral antagonism
- Biased agonism
- Inverse agonism
- Allosteric inhibition
Correct Answer: Biased agonism
Q21. Which receptor type commonly undergoes ligand-induced dimerization as part of activation and regulation?
- G-protein-coupled receptors (GPCRs)
- Toll-like receptors only
- Receptor tyrosine kinases (RTKs)
- Nicotinic ion channels exclusively
Correct Answer: Receptor tyrosine kinases (RTKs)
Q22. Desensitization that is rapidly reversible within minutes and does not require receptor internalization is called:
- Slow downregulation
- Rapid homologous desensitization (phosphorylation-dependent)
- Transcriptional downregulation
- Proteasomal degradation
Correct Answer: Rapid homologous desensitization (phosphorylation-dependent)
Q23. Which clinical phenomenon is most directly linked to receptor downregulation in chronic therapy?
- Improved drug potency over time
- Tolerance requiring higher doses for same effect
- Immediate hypersensitivity reactions
- Spontaneous receptor activation
Correct Answer: Tolerance requiring higher doses for same effect
Q24. In receptor pharmacology, KD represents:
- The concentration of ligand producing half-maximal response
- The dissociation constant reflecting ligand affinity for the receptor
- The maximum effect achievable by an agonist
- The total receptor number in a tissue
Correct Answer: The dissociation constant reflecting ligand affinity for the receptor
Q25. Receptor trafficking to lipid rafts can influence signaling by:
- Excluding receptors from interacting partners and altering downstream pathways
- Always causing receptor degradation
- Preventing ligand binding permanently
- Increasing mRNA transcription of receptors
Correct Answer: Excluding receptors from interacting partners and altering downstream pathways
Q26. Which statement best characterizes noncompetitive antagonists?
- They bind reversibly to the same site as agonists and shift dose–response curves rightward
- They reduce maximal response and are not overcome by increasing agonist concentration
- They increase the potency of agonists
- They only act on intracellular receptors
Correct Answer: They reduce maximal response and are not overcome by increasing agonist concentration
Q27. Which molecular event often follows GPCR phosphorylation and precedes lysosomal degradation?
- Immediate transcriptional activation
- Recruitment of endocytic machinery and internalization
- Direct ubiquitin-independent proteasomal cleavage at the membrane
- Methylation of receptor cytoplasmic domains
Correct Answer: Recruitment of endocytic machinery and internalization
Q28. Allosteric modulators that enhance the effect of an agonist are called:
- Negative allosteric modulators (NAMs)
- Inverse agonists
- Positive allosteric modulators (PAMs)
- Neutral antagonists
Correct Answer: Positive allosteric modulators (PAMs)
Q29. Which describes a pharmacological strategy to reduce receptor-mediated tachyphylaxis?
- Continuous high-dose agonist infusion without breaks
- Pulsatile dosing or drug holidays to allow receptor resensitization
- Using irreversible agonists exclusively
- Avoiding combination therapy with antagonists
Correct Answer: Pulsatile dosing or drug holidays to allow receptor resensitization
Q30. Why is understanding receptor regulation important in drug development?
- It is only relevant for toxicology, not therapeutic design
- It informs dosing, predicts tolerance, guides target selection, and minimizes adverse effects
- It replaces the need for clinical trials
- It ensures drugs will never produce side effects
Correct Answer: It informs dosing, predicts tolerance, guides target selection, and minimizes adverse effects
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
Mail- Sachin@pharmacyfreak.com